1. Field of the Invention
The present invention relates to the field of veterinary medicine, in particular to infectious diseases. Moreover, the present invention relates to a method for reducing concomitant infections in pigs caused by pathogens other than PCV-2.
2. Background
In 1996 a new emerging disease termed “Postweaning Multisystemic Wasting Syndrome” (PMWS) was described in reference to cases observed in Canada five years earlier (Clark T. Pathology of the Postweaning Multisystemic Wasting Syndrome of Pigs. 1996 p. 22-5). Porcine cirocvirus type 2 (PCV2) was identified as an essential causative agent of this disease syndrome. PMWS has meanwhile been observed in virtually all regions of the world that produce pigs (Brunborg I M, Moldal T, Jonassen C M. J Virol Methods 2004 Dec. 15; 122(2):171-8). Pigs 5 to 15 weeks of age are most commonly affected (Allan G, McNeilly F. PMWS/PCVD: Diagnosis, Disease and Control: What do we know? 2006 Jul. 16-2006 Jul. 19; 2006; Allan G M, et al., Vet Microbiol 2004 Feb. 4; 98(2):165-8; Chae C. Vet J 2004 July; 168(1):41-9). Clinical signs include a marked increase in the mortality rate, wasting, generalized enlargment of lymphnodes, respiratory signs, and occasionally pallor, jaundice and diarrhoea (Chae C. Vet J 2005 May; 169(3):326-36; Segales J. et al. Vet Microbiol 2004 Feb. 4; 98(2):151-8). These clinical signs are not all seen at the same time in a single PMWS affected pig herd but it appears that the expression of clinical signs is indirectly linked to farm-specific co-pathogens that preferentially target different organ systems (Krakowka S. et al., Vet Pathol 2001 January; 38(1):31-42). Epidemiological investigations have shown that porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), porcine parvovirus (PPV), Haemophilus parasuis, Actinobacillus pleuropneumoniae (APP), Streptococcus suis and Mycoplasma hyopneumoniae (Chae C. Vet J 2004 July; 168(1):41-9) are most commonly seen in combination with the disease syndrome.
For the production of PMWS activation of the immune system has been postulated to be the pivotal event (Krakowka S. et al., Vet Pathol 2001 January; 38(1):31-42). While the experimental inoculation with PCV2 alone did only produce clinically asymptomatic infections and a very modest histologic evidence of inflammation the dual infection with PCV2 and PPV or PRRSV resulted in more severe clinical signs, gross and histological lesions, a wider spread and a higher PCV2 viral load within affected tissues. These findings seem to be predominantly caused by PCV2 since infection with PRRSV or PPV alone did not result in comparable clinical signs or lesions (Allan et al., J Comp Pathol 1999 July; 121(1):1-11; Allan G M, et al., Arch Virol 2000; 145(11):2421-9; Harms P A, et al., Vet Pathol 2001 September; 38(5):528-39; Krakowka S, et al., Vet Pathol 2000 May; 37(3):254-63; Ostanello F, et al., Vet Microbiol 2005 Jul. 1; 108(3-4):179-86; Rovira A, et al., J Virol 2002 April; 76(7):3232-9). In addition, a similar increase in disease severity could also be achieved in the absence of other co-infecting agents if pigs were immunostimulated with keyhole limpet hemocyanin in incomplete Freund's adjuvant (KLH/ICFA) (Krakowka S. et al., Vet Pathol 2001 January; 38(1):31-42).
The effects of PCV2 on the pig immune system are not fully known. It has been reported that the main target cells for PCV2 replication are the monocyte/macrophage lineage as well as other antigen presenting cells such as follicular dendritic cells (Darwich L, et al., Arch Virol 2004 May; 149(5):857-74). Several studies suggested that PCV2 infects dividing cells, macrophages and B lymphocytes, inducing apoptosis of the B cells that leads to the damage of lymphoid tissues resulting in extensive lymphocyte depletion (Darwich L, et al., Arch Virol 2004 May; 149(5):857-74). Particularly PMWS affected pigs show histiocytic infiltration and lymphocyte depletion of both follicle centers and parafollicular zones, symptoms associated with the presence of PCV2 (Segales J. et al. Vet Microbiol 2004 Feb. 4; 98(2):151-8; Darwich L, et al., Arch Virol 2004 May; 149(5):857-74). These facts have led some to suggest that PCV2 infection might cause immunosuppression (Darwich L, et al., Arch Virol 2004 May; 149(5):857-74; Krakowka S, et al., Viral Immunol 2002; 15(4):567-82).
Approaches to treat PCV2 infections, in particular PMWS, based on a DNA vaccine are described in U.S. Pat. No. 6,703,023. In WO 03/049703 production of a live chimeric vaccine is described, comprising a PCV1 backbone in which an immunogenic gene of a pathogenic PCV2 strains replaces a gene of the PCV1 backbone. WO99/18214 has provided several PCV2 strains and procedures for the preparation of a killed PCV2 vaccine. An effective ORF-2 based subunit vaccine has been reported in WO06/072065. Any of such vaccines are intended to be used for the vaccination/treatment of swine against PMWS.
No reports exist about the potential impact of PCV2 infections on the incidence of concomitant infections caused by various swine relevant pathogens. Particularly, nothing is reported about the potential impact of PCV2 on specific pathogens, such as Actinobacillus pleuropneumoniae, Haemophilus parasuis, Mycoplasma hyorhinis, Pasteurella multocida, PRRSV, Salmonella spp., SIV or Strepococcus suis. Moreover, even if different PCV2 vaccines are known for a short time, their impact on concomitant infections other than PCV2 in swine is yet not known.